Role of Infliximab in Ulcerative Colitis

Abstract

Purpose: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor-alpha, is an established treatment for Crohn's disease. Several recent studies of infliximab in patients with ulcerative colitis (UC) have yielded conflicting results. We conducted a systematic review to assess the efficacy of infliximab in ulcerative colitis. Methods: MEDLINE (from 1966–2006) and abstracts of gastroenterology scientific meetings in the last 5 years were searched (search date June 2006). Open label and randomized control trials in adult subjects were included. Standard forms were used to extract data regarding study design, duration of study, outcome measures, and adverse effects by two independent reviewers. Results: 9 studies satisfied our inclusion criteria: 5 randomized control trials(RCTs) [829 pts] and 4 open label trials [47 pts]. Significant heterogeneity was present among the studies. 3 RCTs evaluated pts with moderate to severe UC, while 1 RCT evaluated pts with acute UC. 1 RCT evaluated the role of infliximab as a rescue therapy in severe UC. 4 RCTs involved pts with steroid refractory UC. In the open label trials, 3 dealt with severe UC while 1 dealt with moderate to severe UC. All of the pts in the open label trials had steroid refractory disease. The dose of infliximab was 5mg/kg in all the studies (RCTs and open label trials), but 2 RCTs also used 10mg/kg of infliximab. 4 RCTs administered 2 or more infusions of infliximab, while all the open label trials administered a single infusion of infliximab. A validated scoring system was used to assess disease activity in all the studies. The primary end point in the trials was evaluated at different time points in all the studies. 2 RCTs found 5mg/kg of infliximab was superior to placebo [OR 5.06; 95% CI 3.09–8.30] in patients with moderate to severe UC at 30 weeks. Similar benefit was noted with a higher dose of 10mg/kg (3.78; 95% CI 2.40–5.96). 3 open label trials also found infliximab induced a clinical response, while 1 open label trial did not. 1 RCT showed that infliximab decreased the rate of colectomy in severe UC patients (OR 4.9; 95% CI 1.4–17). Infliximab was well tolerated in all the studies. Conclusions: Infliximab induces clinical remission in patients with active UC. The optimal dose is 5mg/kg. Additionally, infliximab may also be useful as a rescue therapy in severe UC. However, more studies are needed to verify findings from these smaller studies.